The mission of the UC Davis Center for Children's Environmental Health (CCEH) is to promote daily interactions among a multidisciplinary team of scientists whose main research interest is to understand the complex web of ettologic factors that contribute to autism. The shared philosophy among Center participants is that a better understanding of the immunological and neurobiological mechanisms associated with this neurodevelopmental disorder can not only lead to a better understanding of the mechanisms that influence it but can also accelerate the discovery of effective intervention strategies. The goals of the CCEH in the next five years are to: (1) better understand the mechanisms by which environmental, immunologic, and molecular factors interact to influence the risk and severity of autism; (2) identify early immunologic, environmental, and genomic markers of susceptibility to autism; (3) develop mouse models of immunologic susceptibility to environmental triggers and define the impact of these triggers on the development of complex behaviors, key brain structures and neurotransmitter receptors relevant to autism (4) translate our research findings into diagnostic tools that can be used in clinical practice to predict early autism risk; and (5) supply the community with accurate and timely information about autism risk factors. The CCEH has organized three interrelated hypothesis-based research projects that are supported by five facility cores (Administrative, COTC, Analytical Chemistry, Molecular Genomics, and Statistics). The Projects are: Project 1, Environmental Epidemiology of autism, will build upon our discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) study. Working closely with COTC and Project 2, newborn bloodspots and a second set of blood samples (CHARGE-BACK study) from CHARGE children will examine the stability over time of these biomarkers. CHARGE-BACK blood samples will also provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants. We will launch a new cohort study called Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) that tracks 200 women at high risk of giving birth to an autistic child, starting from early pregnancy and following the pregnancies and the babies to the age of three years. Project 2, Immunological Susceptibilities in Autism, will work dosely with Project 1 to test the overall hypothesis that autistic children have fundamental defects in cellular immunity that ultimately lead to abnormalities in immune dysfunction and heightened susceptibility to environmental triggers. Project 3, Models of Neurodevelopmental Susceptibility, will develop and use mouse models to understand the relationships between immune system dysfunction and perinatal exposure to environmental toxicants in the development of neurobehavioral disorders in sociability and seizure susceptibility. Working closely with Project 2, we will test mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity to determine how perinatal exposures to methylmercury, noncoplanar PCB, or polybrominated diphenyl ether 47 (BDE 47) influence brain development, complex social behaviors, and immune system function.